Interactions of dopaminergic and peptidergic factors in the control of prolactin release.
Oxytocin (OT) has been shown to play a role in the control of physiological PRL release and has been demonstrated to have a direct effect on the pituitary to stimulate PRL secretion. Administration of OT into the third ventricle, however, lowers PRL levels. This reduction could be mediated by either an inhibition of the release of endogenous OT into the hypohysial portal circulation or via an alteration in the release of some other PRL releasing (PRF) or PRL release-inhibiting (PIF) factor. In order to determine if centrally administered OT lowers PRL levels by increasing secretion of dopamine (DA) into the portal circulation, endogenous dopaminergic tone was blocked by injection of the DA antagonist domperidone (DOM). Subcutaneous administration of DOM resulted in elevated PRL levels which could be further augmented by iv infusion of OT (at 0.01 or 0.1 microgram OT/kg.min) or partially, but significantly, reduced by pretreatment with anti-OT antiserum (0.75 ml) indicating that under conditions of DA blockade, OT (which has little PRF activity during conditions of normal dopaminergic tone) can stimulate PRL secretion by a direct pituitary action. Treatment with DOM did not prevent, however, the reduction in PRL levels produced by central administration of OT (2 micrograms). This suggests that the effect of OT to alter PRL secretion when administered into the third ventricle was not mediated via an increase in DA release into the portal circulation. Furthermore, central administration of the OT antagonist CAV-259 (1-deamino-2-D-Trp-4-Val-8-Orn-OT) after DOM treatment resulted in a significant increase in PRL secretion indicating that endogenous levels of OT within the hypothalamus inhibit PRL secretion through a nondopaminergic mechanism. This stimulatory effect of the OT antagonist was not blocked by pretreatment with anti-OT antiserum (iv) which had been demonstrated previously to reduce the PRL surges in lactating mothers and steroid-primed ovariectomized rats, as well as to block the increase in PRL secretion seen after central administration of vasoactive intestinal peptide (VIP). Thus the central effect of OT to alter PRL secretion was probably not due to a change in the release of OT into the portal circulation. Intravenous administration of a VIP antagonist (D-4-Cl-6-Phe-17-Leu-VIP, previously demonstrated to be capable of reducing the PRL surge seen in lactating mothers) into DOM-treated rats does not alter PRL levels but blocks the ability of central administration of the OT antagonist CAV-259 to increase PRL levels under these conditions.(ABSTRACT TRUNCATED AT 400 WORDS)
Mogg
R J
RJ
Department of Anatomy and Neurobiology, University of Missouri, School of Medicine, Columbia 65212.
Samson
W K
WK
D000818:Animals; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists; D007031:Hypothalamus / Q000502:physiology; D007700:Kinetics; D008297:Male; D009479:Neuropeptides / Q000502:physiology*; D010121:Oxytocin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology
D018492:Dopamine Antagonists; D009479:Neuropeptides; C048507:vasoactive intestinal peptide, 4-chloro-Phe(6)-Leu(17)-; D014660:Vasoactive Intestinal Peptide; D010121:Oxytocin; D004294:Domperidone; D011388:Prolactin; C062666:1-deamino-2-Trp-4-Val-8-Orn-OT; D004298:Dopamine